Periodontitis is a common inflammatory disorder of the oral cavity characterized by the osteoclastic resorption of alveolar bone and the premature loss of teeth. Despite its widespread occurrence, the mechanisms underlying alveolar bone loss in this disease complex and most other focal osteopenic disorders remain poorly understood. This lack of knowledge is, to a large extent, a reflection of the inadequacies inherent in available experimental systems which have hampered critical examination of the cellular mechanisms of bone resorption and those factors which influence it. We have developed an experimental system using mononuclear phagocytes which should circumvent these limitations. Mononuclear phagocytes are a characteristic feature of chronic inflammatory lesions. We recently reported that human monocytes, in vitro, resorb bone matrix in an osteoclastlike manner. We have now shown that this process can be precisely quantitated and is responsive to the classic bone-seeking agents, parathyroid hormone, calcitonin and 1,25 dihydroxycholecalciferol. We propose to use this system to: (a) characterize the major biochemical parameters of bone resorption by mononuclear phagocytes; (b) determine whether the resorptive activities of the cells can be modulated by agents involved in the inflammatory process and skeletal homeostasis, (c) determine the extent to which the skeletal matrix dictates the resorptive activity of the mononuclear phagocytes; and (d) determine whether the defects in bone remodeling observed in patients and experimental animals with severe periodontitis, uremia, osteopetrosis or vitamin D-depletion are demonstrable in their mononuclear phagocytes.